The field of neuroendocrine research in depression has generally concentrated on measuring variables and relating them either to diagnosis (e.g., TRH stimulation test in depression versus schizophrenia) or treatment response (the use of T3 as an adjunctive antidepressant). What is needed is data examining various thyroid parameters in various mood states in the same subject in order to understand the relationship among these variables, and to explore state versus trait variables. The proposed project will study 40 subjects with major depressive disorder, using T3 and T4 assays, TRH stimulation tests, reverse T3 assays, dexamethasone suppression tests, prior to treatment. Following four weeks of imipramine treatment and sequential weight measurements, all tests will be repeated. Subjects with less than 50% improvement will then participate in a four week double-blind cross over trial using T3 as an adjunctive antidepressant, following which the test battery will again be repeated. This project may then be able to clarify thyroid parameter predictors of imipramine response and T3 adjunctive response. It will provide data on rT3 levels in depression and the change in rT3 levels with symptom change. It will also shed light on the relationship among the TRH stimulation test, rT3 levels and antidepressant response.